Papain degrades tight junction proteins of human keratinocytes in vitro and sensitizes C57BL/6 mice via the skin independent of its enzymatic activity or TLR4 activation

Caroline Stremnitzer, Krisztina Manzano-Szalai, Anna Willensdorfer, Philipp Starkl, Mario Pieper, Peter König, Michael Mildner, Erwin Tschachler, Ursula Reichart, Erika Jensen-Jarolim

Abstract

Papain is commonly used in food, pharmaceutical, textile, and cosmetic industries and is known to induce occupational allergic asthma. We have previously shown that the papain-like cysteine protease Dermatophagoides pteronyssinus 1 from house dust mite exhibits percutaneous sensitization potential. We aimed here to investigate the potential of papain itself in epicutaneous sensitization. The effects of papain on tight junction (TJ) proteins were tested in vitro in human primary keratinocytes. Using C57BL/6 wild-type and Toll-like receptor 4 (TLR4)-deficient mice, we analyzed the sensitization potential of papain, its effects on the skin barrier, and immune cell recruitment. Our results show that papain affects the skin barrier by increasing transepidermal water loss, degrading TJ proteins and inducing vasodilation. When topically applied, papain exhibited a high epicutaneous inflammatory potential by recruiting neutrophils, mast cells, and CD3-positive cells and by induction of a TH2-biased antibody response. However, its high potency for specific sensitization via the skin was TLR4 independent and, in spite of its capacity to degrade epidermal TJ proteins, does not rely on its enzymatic function. From our data, we conclude that papain has all features to act as a strong allergen via the skin.
Original languageEnglish
Title of host publicationJournal of Investigative Dermatology
Number of pages11
PublisherNature Publishing Group
Publication date18.07.2015
Pages1790-1800
ISBN (Print)1523-1747 (Electronic)\r0022-202X (Linking)
DOIs
Publication statusPublished - 18.07.2015

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